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染色体外环状DNA(Extrachromosomal circular DNA,eccDNA)是驱动肿瘤进展与治疗耐药的关键因素。它能够携带癌基因与耐药基因，并通过非孟德尔遗传机制在细胞分裂中随机不均匀分配，快速产生遗传异质性，促进耐药亚克隆的扩增。本文对eccDNA介导的癌症耐药的生物学基础和核心机制进行了综述：在形成机制方面，染色体碎裂、断裂-融合-桥循环以及非同源末端连接修复等途径共同促进eccDNA的产生。在作用机制上，eccDNA通过多种方式（癌基因的动态扩增、直接或间接调控与肿瘤耐药和生存相关的信号通路以及表观遗传重塑等）来推动肿瘤适应治疗压力。在临床转换与运用上，eccDNA可以动态监测肿瘤的治疗反应及耐药性的产生，而且根据其生命周期或者功能特性设计的靶向治疗也可与现有的肿瘤疗法联合使用，从而克服耐药性。但该领域存在一些挑战，例如eccDNA的检测技术尚未标准化，其和肿瘤微环境之间的相互作用机制也未阐明。未来，我们需要依靠多学科的交叉融合和技术的不断创新，持续推进eccDNA研究结果的临床转化，为解决癌症耐药性提供切实可行的方法。
Abstract：Extrachromosomal circular DNA(eccDNA) is an important reason for the development of cancer and drug resistance. Oncogenes and drug-resistance genes are carried on eccDNA; They do not follow Mendelian inheritance in cell division and are therefore distributed unevenly. It is genetically diverse and has resulted in the spread of resistant subclones. The biological basis and essential mechanisms of eccDNA-mediated resistance to anticancer drugs will be explained in this paper. In terms of the mechanisms of their formation, chromothripsis, breakage-fusion-bridge cycles and non-homologous end joining repair pathways all result in the production of eccDNA. There are many reasons for the development of tumour drug resistance due to changes in eccDNA, such as an increase in oncogenes, direct and indirect modification of the signal-transduction pathway of drug resistance and survival, and epigenetic modification. In terms of clinical translation and application, eccDNA enables real-time dynamic monitoring of therapeutic response and the emergence of drug resistance. Targeted therapy for eccDNA can be combined with conventional cancer treatment at any time in life and under different conditions to deal with drug resistance. However, this area has problems; That is to say, there are no standardised detection methods for eccDNA and its mechanism of association with the tumour microenvironment is unknown. In the future, we will continue to use various disciplines and new technologies to advance the clinical application of eccDNA research and provide concrete, effective ways to treat drug-resistant cancer.
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基本信息:
中图分类号:R730
引用信息:
[1]李华茜,陈慧,万绍贵.染色体外环状DNA在癌症耐药中的作用及临床意义[J].赣南医科大学学报().
基金信息:
江西省自然科学基金重点项目(20244BAB28047);江西省自然科学基金项目(20244BAB28030)
2026-07-01
2026-07-01
2026-07-01